Advances in Gastric Cancer Management: Signaling Pathways, Emerging Diagnostic and Therapeutic Strategies
Abstract
Background:
Gastric cancer (GC) is among the most common malignancies worldwide and represents a major cause of cancer-related mortality. The incidence of GC varies significantly across regions due to genetic predisposition, environmental exposure, dietary habits, and infectious agents, particularly Helicobacter pylori. Despite its high prevalence, GC is often diagnosed at an advanced stage because of nonspecific or absent early clinical symptoms.
Objective:
The objective of this review is to provide a comprehensive overview of the epidemiology, etiology, risk factors, molecular mechanisms, diagnostic biomarkers, and emerging therapeutic strategies for gastric cancer.
Methods:
Relevant literature was reviewed to analyze the role of key molecular signaling pathways involved in gastric carcinogenesis, progression, metastasis, and therapeutic response. Current diagnostic tools, biomarkers, and treatment approaches—including conventional therapies, alternative systems of medicine, nanotechnology-based interventions, and ongoing clinical research—were evaluated.
Results:
Recent molecular classifications have highlighted the critical involvement of signaling pathways such as EGFR/HER2, p53, PI3K, and related pathways in GC development and progression. The identification of biomarkers, including circulating tumor cells and ribonucleic acids, has improved diagnostic accuracy. Advances in targeted therapy and nanotechnology-based drug delivery systems have demonstrated potential in enhancing treatment efficacy and reducing adverse effects.
Conclusion:
Gastric cancer remains a serious global health concern with limited survival outcomes despite advances in treatment. Improved understanding of molecular signaling pathways and biomarker-based diagnostics offers promising opportunities for early detection and targeted therapy. Continued research into innovative preventive and therapeutic approaches is essential for patients with gastric cancer.
Get full access to this article
View all access and purchase options for this article.
References
1. Tong G, Peng T, Chen Y, et al. Effects of GLP-1 receptor agonists on biological behavior of colorectal cancer cells by regulating PI3K/AKT/mTOR signaling pathway. Front Pharmacol, 2022; 13:901559.
2. Xu W-X, Qu Q, Zhuang H-H, et al. The burgeoning significance of liquid-liquid phase separation in the pathogenesis and therapeutics of cancers. Int J Biol Sci, 2024; 20(5):1652–1668.
3. Wu T, Zhao Y, Zhang X, et al. Short-chain acyl post-translational modifications in cancers: Mechanisms, roles, and therapeutic implications. Cancer Commun (Lond), 2025; 45(10):1247–1284.
4. Guo L, Ding J, Zhou W. Harnessing bacteria for Tumor therapy: Current advances and challenges. Chinese Chemical Letters, 2024; 35(2):108557.
5. Jenke R, Oliinyk D, Zenz T, et al. HDAC inhibitors activate lipid peroxidation and ferroptosis in gastric cancer. Biochem Pharmacol, 2024; 225:116257.
6. Zhang Z, Shao S, Luo H, et al. The functions of cuproptosis in gastric cancer: Therapy, diagnosis, prognosis. Biomed Pharmacother, 2024; 177:117100.
7. Chen J, Chen J, Li Z, et al. The apoptotic effect of apigenin on human gastric carcinoma cells through mitochondrial signal pathway. Tumour Biol, 2014; 35(8):7719–7726.
8. Screening P, Board PE. Stomach (Gastric) Cancer Prevention (PDQ®). PDQ Cancer Information Summaries [Internet]: National Cancer Institute (US); 2024.
9. Zheng Q, Zheng H, Liu Z, et al. Current status and future potential of Radiomics in the management of patients with gastric cancer. Arnm, 2025; 3(2):24–38.
10. Jing R, Jiang Z, Tang X. Advances in millimeter-wave treatment and its biological effects development. Int J Mol Sci, 2024; 25(16):8638.
11. Pratas A, Malhão B, Palma R, et al. Effects of apigenin on gastric cancer cells. Biomed Pharmacother, 2024; 172:116251.
12. Liu Z, Sun L, Zhu W, et al. Disulfidptosis signature predicts immune microenvironment and prognosis of gastric cancer. Biol Direct, 2024; 19(1):65.
13. Zeng Q, Chen C, Chen C, et al. Serum Raman spectroscopy combined with convolutional neural network for rapid diagnosis of HER2-positive and triple-negative breast cancer. Spectrochim Acta A Mol Biomol Spectrosc, 2023; 286:122000.
14. Yang H, Li Q, Chen X, et al. Targeting SOX13 inhibits assembly of respiratory chain supercomplexes to overcome ferroptosis resistance in gastric cancer. Nat Commun, 2024; 15(1):4296.
15. Hu B, El Hajj N, Sittler S, et al. Gastric cancer: Classification, histology and application of molecular pathology. J Gastrointest Oncol, 2012; 3(3):251–261.
16. Li Y, Xue XW, Luo YF, et al. Clinicopathologic features of gastric adenocarcinoma based on the revised Lauren’s classification. Zhonghua Bing Li Xue Za Zhi, 2018; 47(7):486–491.
17. Qiu M, Zhou Y, Zhang X, et al. Lauren classification combined with HER2 status is a better prognostic factor in Chinese gastric cancer patients. BMC Cancer, 2014; 14:823.
18. Klein CA. Cancer progression and the invisible phase of metastatic colonization. Nat Rev Cancer, 2020; 20(11):681–694.
19. Eissa S, Swellam M, el-Mosallamy H, et al. Diagnostic value of urinary molecular markers in bladder cancer. Anticancer Res, 2003; 23(5b):4347–4355.
20. Cao Y, Wang D, Mo G, et al. Gastric precancerous lesions: Occurrence, development factors, and treatment. Front Oncol, 2023; 13:1226652.
21. Sexton RE, Al Hallak MN, Diab M, et al. Gastric cancer: A comprehensive review of current and future treatment strategies. Cancer Metastasis Rev, 2020; 39(4):1179–1203.
22. Sitarz R, Skierucha M, Mielko J, et al. Gastric cancer: Epidemiology, prevention, classification, and treatment. Cancer Manag Res, 2018; 10:239–248.
23. Fu B, Liu W, Wang Y, et al. Design and synthesis of Thiourea-Conjugating organic arsenic D-Glucose with anticancer activities. Molecules, 2024; 29(12):2850.
24. Hashemi M, Aparviz R, Beickzade M, et al. Advances in RNAi therapies for gastric cancer: Targeting drug resistance and nanoscale delivery. Biomed Pharmacother, 2023; 169:115927.
25. Luo G, Zhang Y, Guo P, et al. Global patterns and trends in stomach cancer incidence: Age, period and birth cohort analysis. Int J Cancer, 2017; 141(7):1333–1344.
26. Lin J-L, Lin J-X, Lin G-T, et al. Global incidence and mortality trends of gastric cancer and predicted mortality of gastric cancer by 2035. BMC Public Health, 2024; 24(1):1763.
27. Cancer IAfRo. WHO classification of tumours of the digestive system. IntAgency for Res on Cancer, 2019.
28. Lauren P. The two histological main types of gastric carcinoma: Diffuse and so-called intestinal-type carcinoma. An attempt at a Histo-Clinical classification. Acta Pathol Microbiol Scand, 1965; 64:31–49.
29. Rugge M, Genta RM, Di Mario F, et al. Gastric cancer as preventable disease. Clin Gastroenterol Hepatol, 2017; 15(12):1833–1843.
30. Graziano F, Humar B, Guilford P. The role of the E-cadherin gene (CDH1) in diffuse gastric cancer susceptibility: From the laboratory to clinical practice. Ann Oncol, 2003; 14(12):1705–1713.
31. Blair VR, McLeod M, Carneiro F, et al. Hereditary diffuse gastric cancer: Updated clinical practice guidelines. Lancet Oncol, 2020; 21(8):e386–e97.
32. Businello G, Galuppini F, Fassan M. The impact of recent next generation sequencing and the need for a new classification in gastric cancer. Best Pract Res Clin Gastroenterol, 2021; 50–51:101730.
33. Zubair M, Owais M, Mahmood T, et al. Enhanced gastric cancer classification and quantification interpretable framework using digital histopathology images. Sci Rep, 2024; 14(1):22533.
34. Fontana MG, La Pinta M, Moneghini D, et al. Prognostic value of Goseki histological classification in adenocarcinoma of the cardia. Br J Cancer, 2003; 88(3):401–405.
35. Martin IG, Dixon MF, Sue-Ling H, et al. Goseki histological grading of gastric cancer is an important predictor of outcome. Gut, 1994; 35(6):758–763.
36. Machlowska J, Baj J, Sitarz M, et al. Gastric cancer: Epidemiology, risk factors, classification, genomic characteristics and treatment strategies. Int J Mol Sci, 2020; 21(11):4012.
37. Hong Z, Wang Y, Chen X, et al. Triphenyl phosphate (TPP) exposure promotes proliferation and migration capabilities of gastric cancer cells: Insights from gene expression and pathway analysis. Ecotoxicol Environ Saf, 2024; 281:116618.
38. Cats A, Meuwissen SG, Forman D, et al. Helicobacter pylori: A true carcinogen? Eur J Gastroenterol Hepatol, 1998; 10(6):447–450.
39. Conteduca V, Sansonno D, Lauletta G, et al. Pylori infection and gastric cancer: State of the art (review). Int J Oncol, 2013; 42(1):5–18.
40. Iizasa H, Nanbo A, Nishikawa J, et al. Epstein-Barr Virus (EBV)-associated gastric carcinoma. Viruses, 2012; 4(12):3420–3439.
41. Vogelaar IP, van der Post RS, Bisseling TM, et al. Familial gastric cancer: Detection of a hereditary cause helps to understand its etiology. Hered Cancer Clin Pract, 2012; 10(1):18.
42. Josefson D. Prophylactic gastrectomy seems to extend life of patients with a family history of stomach cancer. Bmj, 2001; 322(7302):1566.4.
43. Ferro A, Rosato V, Rota M, et al. Meat intake and risk of gastric cancer in the Stomach cancer Pooling (StoP) project. Int J Cancer, 2020; 147(1):45–55.
44. Islami F, Boffetta P, Ren JS, et al. High-temperature beverages and foods and esophageal cancer risk–a systematic review. Int J Cancer, 2009; 125(3):491–524.
45. Hu M-L, Yeh K-T, Lin P-M, et al. Deregulated expression of circadian clock genes in gastric cancer. BMC Gastroenterol, 2014; 14:67.
46. Praud D, Rota M, Pelucchi C, et al. Cigarette smoking and gastric cancer in the Stomach Cancer Pooling (StoP) Project. Eur J Cancer Prev, 2018; 27(2):124–133.
47. Fox JG, Dangler CA, Taylor NS, et al. High-salt diet induces gastric epithelial hyperplasia and parietal cell loss, and enhances Helicobacter pylori colonization in C57BL/6 mice. Cancer Res, 1999; 59(19):4823–4828.
48. Tsugane S. Salt, salted food intake, and risk of gastric cancer: Epidemiologic evidence. Cancer Sci, 2005; 96(1):1–6.
49. Lin X-J, Wang C-P, Liu X-D, et al. Body mass index and risk of gastric cancer: A meta-analysis. Jpn J Clin Oncol, 2014; 44(9):783–791.
50. Thrift AP, Nguyen TH. Gastric cancer epidemiology. Gastrointest Endosc Clin N Am, 2021; 31(3):425–439.
51. Noto JM, Peek RM Jr. The gastric microbiome, its interaction with Helicobacter pylori, and its potential role in the progression to stomach cancer. PLoS Pathog, 2017; 13(10):e1006573.
52. Meng C, Bai C, Brown TD, et al. Human gut microbiota and gastrointestinal cancer. Genomics Proteomics Bioinformatics, 2018; 16(1):33–49.
53. Maldonado-Contreras A, Goldfarb KC, Godoy-Vitorino F, et al. Structure of the human gastric bacterial community in relation to Helicobacter pylori status. Isme J, 2011; 5(4):574–579.
54. Aviles-Jimenez F, Vazquez-Jimenez F, Medrano-Guzman R, et al. Stomach microbiota composition varies between patients with non-atrophic gastritis and patients with intestinal type of gastric cancer. Sci Rep, 2014; 4:4202.
55. Dicksved J, Lindberg M, Rosenquist M, et al. Molecular characterization of the stomach microbiota in patients with gastric cancer and in controls. J Med Microbiol, 2009; 58(Pt 4):509–516.
56. Wang L, Zhou J, Xin Y, et al. Bacterial overgrowth and diversification of microbiota in gastric cancer. Eur J Gastroenterol Hepatol, 2016; 28(3):261–266.
57. Serban DE. Gastrointestinal cancers: Influence of gut microbiota, probiotics and prebiotics. Cancer Lett, 2014; 345(2):258–270.
58. Jaye K, Li CG, Bhuyan DJ. The complex interplay of gut microbiota with the five most common cancer types: From carcinogenesis to therapeutics to prognoses. Crit Rev Oncol Hematol, 2021; 165:103429.
59. Wei L, Sun J, Zhang N, et al. Noncoding RNAs in gastric cancer: Implications for drug resistance. Mol Cancer, 2020; 19(1):62.
60. Anwar MM, Albanese C, Hamdy NM, et al. Rise of the natural red pigment ‘Prodigiosin’ as an immunomodulator in cancer. Cancer Cell Int, 2022; 22(1):419.
61. Wu M, Yuan S, Liu K, et al. Gastric cancer signaling pathways and therapeutic applications. Technol Cancer Res Treat, 2024; 23:15330338241271935.
62. Lei Z-N, Teng Q-X, Tian Q, et al. Signaling pathways and therapeutic interventions in gastric cancer. Signal Transduct Target Ther, 2022; 7(1):358.
63. Bartholomeusz C, Gonzalez-Angulo AM. Targeting the PI3K signaling pathway in cancer therapy. Expert Opin Ther Targets, 2012; 16(1):121–130.
64. Michl P, Downward J. Mechanisms of disease: PI3K/AKT signaling in gastrointestinal cancers. Z Gastroenterol, 2005; 43(10):1133–1139.
65. Sukawa Y, Yamamoto H, Nosho K, et al. Alterations in the human epidermal growth factor receptor 2-phosphatidylinositol 3-kinase-v-Akt pathway in gastric cancer. World J Gastroenterol, 2012; 18(45):6577–6586.
66. Albertson DG. Gene amplification in cancer. Trends Genet, 2006; 22(8):447–455.
67. Schwab M. Amplification of oncogenes in human cancer cells. Bioessays, 1998; 20(6):473–479.
68. Shi J, Yao D, Liu W, et al. Highly frequent PIK3CA amplification is associated with poor prognosis in gastric cancer. BMC Cancer, 2012; 12:50.
69. Guo CY, Xu XF, Wu JY, et al. PCR-SSCP-DNA sequencing method in detecting PTEN gene mutation and its significance in human gastric cancer. World J Gastroenterol, 2008; 14(24):3804–3811.
70. Wen YG, Wang Q, Zhou CZ, et al. Mutation analysis of tumor suppressor gene PTEN in patients with gastric carcinomas and its impact on PI3K/AKT pathway. Oncol Rep, 2010; 24(1):89–95.
71. Tamura G. Alterations of tumor suppressor and tumor-related genes in the development and progression of gastric cancer. World J Gastroenterol, 2006; 12(2):192–198.
72. Shi J, Qu YP, Hou P. Pathogenetic mechanisms in gastric cancer. World J Gastroenterol, 2014; 20(38):13804–13819.
73. Zhang XL, Yang YS, Xu DP, et al. Comparative study on overexpression of HER2/neu and HER3 in gastric cancer. World J Surg, 2009; 33(10):2112–2118.
74. Reyes VE. Helicobacter pylori and its role in gastric cancer. Microorganisms, 2023; 11(5):1312.
75. Han S-H, Lee J-H, Woo J-S, et al. Myricetin induces apoptosis and autophagy in human gastric cancer cells through inhibition of the PI3K/Akt/mTOR pathway. Heliyon, 2022; 8(5):e09309.
76. Xiang F, Wu K, Liu Y, et al. Omental adipocytes enhance the invasiveness of gastric cancer cells by oleic acid-induced activation of the PI3K-Akt signaling pathway. Int J Biochem Cell Biol, 2017; 84:14–21.
77. Li W, Wei J, Cheng M, et al. Unveiling promising targets in gastric cancer therapy: A comprehensive review. Mol Ther Oncol, 2024; 32(3):200857.
78. Mossmann D, Park S, Hall MN. mTOR signalling and cellular metabolism are mutual determinants in cancer. Nat Rev Cancer, 2018; 18(12):744–757.
79. Kim EK, Choi EJ. Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta, 2010; 1802(4):396–405.
80. Young A, Lyons J, Miller AL, et al. Ras signaling and therapies. Adv Cancer Res, 2009; 102:1–17.
81. Lee SH, Lee JW, Soung YH, et al. BRAF and KRAS mutations in stomach cancer. Oncogene, 2003; 22(44):6942–6945.
82. Yoo J, Park SY, Robinson RA, et al. ras Gene mutations and expression of Ras signal transduction mediators in gastric adenocarcinomas. Arch Pathol Lab Med, 2002; 126(9):1096–1100.
83. Liang B, Wang S, Zhu XG, et al. Increased expression of mitogen-activated protein kinase and its upstream regulating signal in human gastric cancer. World J Gastroenterol, 2005; 11(5):623–628.
84. Shi J, Zhang G, Yao D, et al. Prognostic significance of aberrant gene methylation in gastric cancer. Am J Cancer Res, 2012; 2(1):116–129.
85. Wang Y-C, Yu Z-H, Liu C, et al. Detection of RASSF1A promoter hypermethylation in serum from gastric and colorectal adenocarcinoma patients. World J Gastroenterol, 2008; 14(19):3074–3080.
86. Endoh M, Tamura G, Honda T, et al. RASSF2, a potential tumour suppressor, is silenced by CpG island hypermethylation in gastric cancer. Br J Cancer, 2005; 93(12):1395–1399.
87. Dammann R, Schagdarsurengin U, Seidel C, et al. The tumor suppressor RASSF1A in human carcinogenesis: An update. Histol Histopathol, 2005; 20:645–663.
88. Zacarias O, Clement CC, Cheng S-Y, et al. Mitomycin C and its analog trigger cytotoxicity in MCF-7 and K562 cancer cells through the regulation of RAS and MAPK/ERK pathways. Chem Biol Interact, 2024; 395:111007.
89. Slesak B, Harlozinska A, Porebska I, et al. Expression of epidermal growth factor receptor family proteins (EGFR, c-erbB-2 and c-erbB-3) in gastric cancer and chronic gastritis. Anticancer Res, 1998; 18(4A):2727–2732.
90. Lee JW, Soung YH, Kim SY, et al. ERBB2 kinase domain mutation in a gastric cancer metastasis. Apmis, 2005; 113(10):683–687.
91. Tanner M, Hollmén M, Junttila TT, et al. Amplification of HER-2 in gastric carcinoma: Association with Topoisomerase IIalpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol, 2005; 16(2):273–278.
92. Kogo R, Mimori K, Tanaka F, et al. Clinical significance of miR-146a in gastric cancer cases. Clin Cancer Res, 2011; 17(13):4277–4284.
93. Nishida N, Mimori K, Fabbri M, et al. MicroRNA-125a-5p is an independent prognostic factor in gastric cancer and inhibits the proliferation of human gastric cancer cells in combination with trastuzumab. Clin Cancer Res, 2011; 17(9):2725–2733.
94. Fenoglio-Preiser CM, Wang J, Stemmermann GN, et al. TP53 and gastric carcinoma: A review. Hum Mutat, 2003; 21(3):258–270.
95. Karaman A, Kabalar ME, Binici DN, et al. Genetic alterations in gastric precancerous lesions. Genet Couns, 2010; 21(4):439–450.
96. Kouraklis G, Katsoulis IE, Theocharis S, et al. Does the expression of cyclin E, pRb, and p21 correlate with prognosis in gastric adenocarcinoma? Dig Dis Sci, 2009; 54(5):1015–1020.
97. Dong Q, Zheng A, Zhai H, et al. Resveratrol mediated the proliferation and apoptosis of gastric cancer cells by modulating the PI3K/Akt/P53 signaling pathway. Biochem Biophys Res Commun, 2024; 723:150186.
98. Zhang H, Xue Y. Wnt pathway is involved in advanced gastric carcinoma. Hepatogastroenterology, 2008; 55(84):1126–1130.
99. Pan KF, Liu WG, Zhang L, et al. Mutations in components of the Wnt signaling pathway in gastric cancer. World J Gastroenterol, 2008; 14(10):1570–1574.
100. Kurayoshi M, Oue N, Yamamoto H, et al. Expression of Wnt-5a is correlated with aggressiveness of gastric cancer by stimulating cell migration and invasion. Cancer Res, 2006; 66(21):10439–10448.
101. Gencer S, Şen G, Doğusoy G, et al. β-Catenin-independent noncanonical Wnt pathway might be induced in gastric cancers. Turk J Gastroenterol, 2010; 21(3):224–230.
102. Resende C, Ristimäki A, Machado JC. Genetic and epigenetic alteration in gastric carcinogenesis. Helicobacter, 2010; 15(Suppl 1):34–39.
103. Jiang Q, Li Y, Cai S, et al. GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progresses of gastric cancer. Acta Pharm Sin B, 2024; 14(2):698–711.
104. van Roy F, Berx G. The cell-cell adhesion molecule E-cadherin. Cell Mol Life Sci, 2008; 65(23):3756–3788.
105. Leckband D, Sivasankar S. Mechanism of homophilic cadherin adhesion. Curr Opin Cell Biol, 2000; 12(5):587–592.
106. Corso G, Seruca R, Roviello F. Gastric cancer carcinogenesis and tumor progression. Ann Ital Chir, 2012; 83(3):172–176.
107. Carneiro P, Fernandes MS, Figueiredo J, et al. E-cadherin dysfunction in gastric cancer–cellular consequences, clinical applications and open questions. FEBS Lett, 2012; 586(18):2981–2989.
108. Leal MF, Lima EM, Silva PNO, et al. Promoter hypermethylation of CDH1, FHIT, MTAP and PLAGL1 in gastric adenocarcinoma in individuals from Northern Brazil. World J Gastroenterol, 2007; 13(18):2568–2574.
109. Corso G, Marrelli D, Roviello F. Familial gastric cancer and germline mutations of E-cadherin. Ann Ital Chir, 2012; 83(3):177–182.
110. Calcagno DQ, Gigek CO, Chen ES, et al. DNA and histone methylation in gastric carcinogenesis. World J Gastroenterol, 2013; 19(8):1182–1192.
111. Li Y, Wang Y, Zou Q, et al. KLF3 transcription activates WNT1 and promotes the growth and metastasis of gastric cancer via activation of the WNT/β-Catenin signaling pathway. Lab Invest, 2023; 103(6):100078.
112. Williams CS, Mann M, DuBois RN. The role of cyclooxygenases in inflammation, cancer, and development. Oncogene, 1999; 18(55):7908–7916.
113. Xue YW, Zhang QF, Zhu ZB, et al. Expression of cyclooxygenase-2 and clinicopathologic features in human gastric adenocarcinoma. World J Gastroenterol, 2003; 9(2):250–253.
114. Shi H, Xu JM, Hu NZ, et al. Prognostic significance of expression of cyclooxygenase-2 and vascular endothelial growth factor in human gastric carcinoma. World J Gastroenterol, 2003; 9(7):1421–1426.
115. Oshima H, Oguma K, Du YC, et al. Prostaglandin E2, Wnt, and BMP in gastric tumor mouse models. Cancer Sci, 2009; 100(10):1779–1785.
116. Murakami M, Naraba H, Tanioka T, et al. Regulation of prostaglandin E2 biosynthesis by inducible membrane-associated prostaglandin E2 synthase that acts in concert with cyclooxygenase-2. J Biol Chem, 2000; 275(42):32783–32792.
117. Gross ND, Boyle JO, Morrow JD, et al. Levels of prostaglandin E metabolite, the major urinary metabolite of prostaglandin E2, are increased in smokers. Clin Cancer Res, 2005; 11(16):6087–6093.
118. Huang RY, Chen GG. Cigarette smoking, cyclooxygenase-2 pathway and cancer. Biochim Biophys Acta, 2011; 1815(2):158–169.
119. Oshima H, Matsunaga A, Fujimura T, et al. Carcinogenesis in mouse stomach by simultaneous activation of the Wnt signaling and prostaglandin E2 pathway. Gastroenterology, 2006; 131(4):1086–1095.
120. Figueiredo C, Garcia‐Gonzalez MA, Machado JC. Molecular pathogenesis of gastric cancer. Helicobacter, 2013; 18(Suppl 1):28–33.
121. Thanos D, Maniatis T. NF-kappa B: A lesson in family values. Cell, 1995; 80(4):529–532.
122. Sasaki N, Morisaki T, Hashizume K, et al. Nuclear factor-kappaB p65 (RelA) transcription factor is constitutively activated in human gastric carcinoma tissue. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 2001; 7:4136–4142.
123. Yamanaka N, Sasaki N, Tasaki A, et al. Nuclear factor-kappaB p65 is a prognostic indicator in gastric carcinoma. Anticancer Res, 2004; 24(2C):1071–1075.
124. Wang K, Shen K, Wang J, et al. BUB1 potentiates gastric cancer proliferation and metastasis by activating TRAF6/NF-κB/FGF18 through m6A modification. Life Sci, 2024; 353:122916.
125. Yan S, Wang Z, Lan D, et al. Circ_PABPC1 promotes the malignancy of gastric cancer through interacting with ILK to activate NF-κB pathway. Exp Cell Res, 2024; 438(2):114058.
126. Elanany MM, Mostafa D, Hamdy NM. Remodeled tumor immune microenvironment (TIME) parade via natural killer cells reprogramming in breast cancer. Life Sci, 2023; 330:121997.
127. Wright K, Ly T, Kriet M, et al. Cancer-Associated fibroblasts: Master tumor microenvironment modifiers. Cancers (Basel), 2023; 15(6):1899.
128. Li Y, Zhong X, Zhang Y, et al. Mesenchymal stem cells in gastric cancer: Vicious but hopeful. Front Oncol, 2021; 11:617677.
129. Chen M, Chen F, Gao Z, et al. CAFs and T cells interplay: The emergence of a new arena in cancer combat. Biomed Pharmacother, 2024; 177:117045.
130. Kim EY, Yoo HM, Song KY, et al. Limited significance of curative surgery in Borrmann type IV gastric cancer. Med Oncol, 2016; 33(7):69.
131. Liu X, Yao L, Qu J, et al. Cancer-associated fibroblast infiltration in gastric cancer: The discrepancy in subtypes pathways and immunosuppression. J Transl Med, 2021; 19(1):325.
132. Fares J, Fares MY, Khachfe HH, et al. Molecular principles of metastasis: A hallmark of cancer revisited. Signal Transduct Target Ther, 2020; 5(1):28.
133. Li P, Zhang H, Chen T, et al. Cancer-associated fibroblasts promote proliferation, angiogenesis, metastasis and immunosuppression in gastric cancer. Matrix Biol, 2024; 132:59–71.
134. Kennel KB, Bozlar M, De Valk AF, et al. Cancer-Associated fibroblasts in inflammation and antitumor immunity. Clin Cancer Res, 2023; 29(6):1009–1016.
135. Sun H, Wang X, Wang X, et al. The role of cancer-associated fibroblasts in tumorigenesis of gastric cancer. Cell Death Dis, 2022; 13(10):874.
136. Li D, Wang Y, Shi C, et al. Targeting GPC3(high) cancer-associated fibroblasts sensitizing the PD-1 blockage therapy in gastric cancer. Ann Med, 2023; 55(1):2189295.
137. Liu Y, Li C, Lu Y, et al. Tumor microenvironment-mediated immune tolerance in development and treatment of gastric cancer. Front Immunol, 2022; 13:1016817.
138. Zhang D, Sun R, Di C, et al. Microdissection of cancer-associated fibroblast infiltration subtypes unveils the secreted SERPINE2 contributing to immunosuppressive microenvironment and immuotherapeutic resistance in gastric cancer: A large-scale study integrating bulk and single-cell transcriptome profiling. Comput Biol Med, 2023; 166:107406.
139. Li D, Xia L, Huang P, et al. Cancer-associated fibroblast-secreted IGFBP7 promotes gastric cancer by enhancing tumor associated macrophage infiltration via FGF2/FGFR1/PI3K/AKT axis. Cell Death Discov, 2023; 9(1):17.
140. Yin SY, Liu YJ, Li JP, et al. Overexpression of FERM domain containing Kindlin 2 (FERMT2) in fibroblasts correlates with EMT and immunosuppression in gastric cancer. Int J Genomics, 2024; 2024:4123737.
141. Kim EK, Yoon SO, Jung WY, et al. Implications of NOVA1 suppression within the microenvironment of gastric cancer: Association with immune cell dysregulation. Gastric Cancer, 2017; 20(3):438–447.
142. Yao L, Hou J, Wu X, et al. Cancer-associated fibroblasts impair the cytotoxic function of NK cells in gastric cancer by inducing ferroptosis via iron regulation. Redox Biol, 2023; 67:102923.
143. Galluzzi L, Vitale I, Aaronson SA, et al. Molecular mechanisms of cell death: Recommendations of the nomenclature committee on cell death 2018. Cell Death Differ, 2018; 25(3):486–541.
144. Martinez-Outschoorn UE, Trimmer C, Lin Z, et al. Autophagy in cancer associated fibroblasts promotes tumor cell survival: Role of hypoxia, HIF1 induction and NFκB activation in the tumor stromal microenvironment. Cell Cycle, 2010; 9(17):3515–3533.
145. Sun C, Fukui H, Hara K, et al. FGF9 from cancer-associated fibroblasts is a possible mediator of invasion and anti-apoptosis of gastric cancer cells. BMC Cancer, 2015; 15:333.
146. Zhang H, Deng T, Liu R, et al. CAF secreted miR-522 suppresses ferroptosis and promotes acquired chemo-resistance in gastric cancer. Mol Cancer, 2020; 19(1):43.
147. Qu X, Liu B, Wang L, et al. Loss of cancer-associated fibroblast-derived exosomal DACT3-AS1 promotes malignant transformation and ferroptosis-mediated oxaliplatin resistance in gastric cancer. Drug Resist Updat, 2023; 68:100936.
148. Liu ZL, Chen HH, Zheng LL, et al. Angiogenic signaling pathways and anti-angiogenic therapy for cancer. Signal Transduct Target Ther, 2023; 8(1):198.
149. Tang D, Gao J, Wang S, et al. Cancer-associated fibroblasts promote angiogenesis in gastric cancer through galectin-1 expression. Tumour Biol, 2016; 37(2):1889–1899.
150. Wang EJ-Y, Chen I-H, Kuo BY-T, et al. Alterations of cytoskeleton networks in cell fate determination and cancer development. Biomolecules, 2022; 12(12):1862.
151. Hall A. The cytoskeleton and cancer. Cancer Metastasis Rev, 2009; 28(1–2):5–14.
152. Lu G, Du R, Dong J, et al. Cancer associated fibroblast derived SLIT2 drives gastric cancer cell metastasis by activating NEK9. Cell Death Dis, 2023; 14(7):421.
153. Brabletz S, Schuhwerk H, Brabletz T, et al. Dynamic EMT: A multi-tool for tumor progression. Embo J, 2021; 40(18):e108647.
154. Satala C-B, Jung I, Kovacs Z, et al. V-set and immunoglobulin domain containing 1 (VSIG1) as an emerging target for epithelial-mesenchymal transition of gastric cancer. Sci Rep, 2022; 12(1):16241.
155. Yuzhalin AE, Lim SY, Kutikhin AG, et al. Dynamic matrisome: ECM remodeling factors licensing cancer progression and metastasis. Biochim Biophys Acta Rev Cancer, 2018; 1870(2):207–228.
156. Liu K, Zhao Q, Li B, et al. Raman spectroscopy: A novel technology for gastric cancer diagnosis. Front Bioeng Biotechnol, 2022; 10:856591.
157. Chen ZD, Zhang PF, Xi HQ, et al. Recent advances in the diagnosis, staging, treatment, and prognosis of advanced gastric cancer: A literature review. Front Med (Lausanne), 2021; 8:744839.
158. Gao H, Bao P, Dai S, et al. Far-Red/Near-Infrared Emissive (1,3-Dimethyl)barbituric acid-based AIEgens for high-contrast detection of metastatic tumors in the lung. Chem Asian J, 2019; 14(6):871–876.
159. Li X, Ai S, Lu X, et al. Nanotechnology-based strategies for gastric cancer imaging and treatment. RSC Adv, 2021; 11(56):35392–35407.
160. Wang S, Chi C, Cheng H, et al. Photothermal adjunctive cytoreductive surgery for treating peritoneal metastasis of gastric cancer. Small Methods, 2018; 2(4):1700368.
161. Tian R, Ma H, Yang Q, et al. Rational design of a super-contrast NIR-II fluorophore affords high-performance NIR-II molecular imaging guided microsurgery. Chem Sci, 2019; 10(1):326–332.
162. Kanazaki K, Sano K, Makino A, et al. Development of anti-HER2 fragment antibody conjugated to iron oxide nanoparticles for in vivo HER2-targeted photoacoustic tumor imaging. Nanomedicine, 2015; 11(8):2051–2060.
163. Zhang K, Du X, Yu K, et al. Application of novel targeting nanoparticles contrast agent combined with contrast-enhanced computed tomography during screening for early-phase gastric carcinoma. Exp Ther Med, 2018; 15(1):47–54.
164. Wang P, Qu Y, Li C, et al. Bio-functionalized dense-silica nanoparticles for MR/NIRF imaging of CD146 in gastric cancer. Int J Nanomedicine, 2015; 10:749–763.
165. Hachani R, Birchall MA, Lowdell MW, et al. Assessing cell-nanoparticle interactions by high content imaging of biocompatible iron oxide nanoparticles as potential contrast agents for magnetic resonance imaging. Sci Rep, 2017; 7(1):7850.
166. Guo H, Zhang Y, Liang W, et al. An inorganic magnetic fluorescent nanoprobe with favorable biocompatibility for dual-modality bioimaging and drug delivery. J Inorg Biochem, 2019; 192:72–81.
167. Shi B, Zhang B, Zhang Y, et al. Multifunctional gap-enhanced Raman tags for preoperative and intraoperative cancer imaging. Acta Biomater, 2020; 104:210–220.
168. Shin U, Kim J, Lee J, et al. Development of (64)Cu-loaded Perfluoropentane Nanodroplet: A potential tumor theragnostic nano-carrier and dual-modality PET-ultrasound imaging agents. Ultrasound Med Biol, 2020; 46(10):2775–2784.
169. Bollschweiler E, Berlth F, Baltin C, et al. Treatment of early gastric cancer in the Western World. World J Gastroenterol, 2014; 20(19):5672–5678.
170. Wakahara T, Ueno N, Maeda T, et al. Impact of gastric cancer surgery in elderly patients. Oncology, 2018; 94(2):79–84.
171. Junttila A, Helminen O, Helmiö M, et al.; Finnish National Esophago-Gastric Cancer Cohort Group. Postoperative delayed emptying after total, subtotal, or distal gastrectomy for gastric cancer: A population-based study. J Gastrointest Surg, 2024; 28(7):1083–1088.
172. Sasako M, Sakuramoto S, Katai H, et al. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol, 2011; 29(33):4387–4393.
173. Jayanathan M, Erwin RP, Molacek N, et al. MAGIC versus MacDonald treatment regimens for gastric cancer: Trends and predictors of multimodal therapy for gastric cancer using the National Cancer Database. Am J Surg, 2020; 219(1):129–135.
174. Schwartz GK, Christman K, Saltz L, et al. A phase I trial of a modified, dose intensive FAMTX regimen (high dose 5-fluorouracil+doxorubicin+high dose methotrexate+leucovorin) with oral uridine rescue. Cancer, 1996; 78(9):1988–1995.
175. Webb A, Cunningham D, Scarffe JH, et al. Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol, 1997; 15(1):261–267.
176. Bölke E, Peiper M, Budach W. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med, 2008; 358(18):1965; author reply 1965.
177. Al-Batran S-E, Homann N, Pauligk C, et al.; FLOT4-AIO Investigators. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): A randomised, phase 2/3 trial. Lancet, 2019; 393(10184):1948–1957.
178. Masuishi T, Kadowaki S, Kondo M, et al. FOLFOX as first-line therapy for gastric cancer with severe peritoneal metastasis. Anticancer Res, 2017; 37(12):7037–7042.
179. Ahn HS, Jeong S-H, Son YG, et al. Effect of neoadjuvant chemotherapy on postoperative morbidity and mortality in patients with locally advanced gastric cancer. Br J Surg, 2014; 101(12):1560–1565.
180. Hamdy NM, Basalious EB, El-Sisi MG, et al. Advancements in current one-size-fits-all therapies compared to future treatment innovations for better improved chemotherapeutic outcomes: A step-toward personalized medicine. Curr Med Res Opin, 2024; 40(11):1943–1961.
181. Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med, 2005; 353(16):1673–1684.
182. Shitara K, Bang Y-J, Iwasa S, et al.; DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in previously treated HER2-Positive gastric cancer. N Engl J Med, 2020; 382(25):2419–2430.
183. Shi F, Liu Y, Zhou X, et al. Disitamab vedotin: A novel antibody-drug conjugates for cancer therapy. Drug Deliv, 2022; 29(1):1335–1344.
184. Peng Z, Liu T, Wei J, et al. Efficacy and safety of a novel anti-HER2 therapeutic antibody RC48 in patients with HER2-overexpressing, locally advanced or metastatic gastric or gastroesophageal junction cancer: A single-arm phase II study. Cancer Commun (Lond), 2021; 41(11):1173–1182.
185. Golan T, Hammel P, Reni M, et al. Overall Survival from the Phase 3 POLO Trial: Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer. American Society of Clinical Oncology; 2021.
186. Hansson LE, Sparén P, Nyrén O. Survival in stomach cancer is improving: Results of a nationwide population-based Swedish study. Ann Surg, 1999; 230(2):162–169.
187. Ferguson FM, Gray NS. Kinase inhibitors: The road ahead. Nat Rev Drug Discov, 2018; 17(5):353–377.
188. Boland PM, Meyer JE, Berger AC, et al. Induction therapy for locally advanced, Resectable Esophagogastric cancer: A phase I trial of Vandetanib (ZD6474), paclitaxel, carboplatin, 5-fluorouracil, and radiotherapy followed by resection. Am J Clin Oncol, 2017; 40(4):393–398.
189. Xie L, Su X, Zhang L, et al. FGFR2 gene amplification in gastric cancer predicts sensitivity to the selective FGFR inhibitor AZD4547. Clin Cancer Res, 2013; 19(9):2572–2583.
190. Fuchs CS, Tomasek J, Yong CJ, et al.; REGARD Trial Investigators. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): An international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet, 2014; 383(9911):31–39.
191. Scott LJ. Apatinib: A review in advanced gastric cancer and other advanced cancers. Drugs, 2018; 78(7):747–758.
192. Li J, Qin S, Xu J, et al. Randomized, double-blind, placebo-controlled phase III trial of Apatinib in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction. J Clin Oncol, 2016; 34(13):1448–1454.
193. Fukuoka S, Hara H, Takahashi N, et al. Regorafenib plus Nivolumab in patients with advanced gastric or colorectal cancer: An open-label, dose-escalation, and dose-expansion phase Ib trial (REGONIVO, EPOC1603). J Clin Oncol, 2020; 38(18):2053–2061.
194. Kawazoe A, Fukuoka S, Nakamura Y, et al. Lenvatinib plus pembrolizumab in patients with advanced gastric cancer in the first-line or second-line setting (EPOC1706): An open-label, single-arm, phase 2 trial. Lancet Oncol, 2020; 21(8):1057–1065.
195. Van Cutsem E, Bang Y-J, Mansoor W, et al. A randomized, open-label study of the efficacy and safety of AZD4547 monotherapy versus paclitaxel for the treatment of advanced gastric adenocarcinoma with FGFR2 polysomy or gene amplification. Ann Oncol, 2017; 28(6):1316–1324.
196. Wainberg ZA, Enzinger PC, Kang Y-K, et al. Randomized double-blind placebo-controlled phase 2 study of bemarituzumab combined with modified FOLFOX6 (mFOLFOX6) in first-line (1L) treatment of advanced gastric/gastroesophageal junction adenocarcinoma (Fig.HT). JCO, 2021; 39(3_suppl):160.
197. Qi C, Gong J, Li J, et al. Claudin18.2-specific CAR T cells in gastrointestinal cancers: Phase 1 trial interim results. Nat Med, 2022; 28(6):1189–1198.
198. LoRusso PM. Inhibition of the PI3K/AKT/mTOR pathway in solid tumors. J Clin Oncol, 2016; 34(31):3803–3815.
199. Nakayama A, Abe H, Kunita A, et al. Viral loads correlate with upregulation of PD-L1 and worse patient prognosis in Epstein-Barr Virus-associated gastric carcinoma. PLoS One, 2019; 14(1):e0211358.
200. Chen L-T, Satoh T, Ryu M-H, et al. A phase 3 study of nivolumab in previously treated advanced gastric or gastroesophageal junction cancer (ATTRACTION-2): 2-year update data. Gastric Cancer, 2020; 23(3):510–519.
201. Shitara K, Van Cutsem E, Bang Y-J, et al. Efficacy and safety of Pembrolizumab or Pembrolizumab plus chemotherapy vs chemotherapy alone for patients with first-line, advanced gastric cancer: The KEYNOTE-062 phase 3 randomized clinical trial. JAMA Oncol, 2020; 6(10):1571–1580.
202. Janjigian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet, 2021; 398(10294):27–40.
203. Tawbi HA, Schadendorf D, Lipson EJ, et al.; RELATIVITY-047 Investigators. Relatlimab and Nivolumab versus Nivolumab in untreated advanced melanoma. N Engl J Med, 2022; 386(1):24–34.
204. Zhang Q, Bi J, Zheng X, et al. Blockade of the checkpoint receptor TIGIT prevents NK cell exhaustion and elicits potent anti-tumor immunity. Nat Immunol, 2018; 19(7):723–732.
205. Cho BC, Abreu DR, Hussein M, et al. Tiragolumab plus atezolizumab versus placebo plus atezolizumab as a first-line treatment for PD-L1-selected non-small-cell lung cancer (CITYSCAPE): Primary and follow-up analyses of a randomised, double-blind, phase 2 study. Lancet Oncol, 2022; 23(6):781–792.
206. Gao D, Liu L, Liu J, et al. Predictive response and outcome of peripheral CD4(+) T cell subpopulations to combined immunotherapy and chemotherapy in advanced gastric cancer patients. Int Immunopharmacol, 2024; 129:111663.
207. Wang Q, Huang Y, Ni Y, et al. siRNA targeting midkine inhibits gastric cancer cells growth and induces apoptosis involved caspase-3,8,9 activation and mitochondrial depolarization. J Biomed Sci, 2007; 14(6):783–795.
208. Lei X-Y, Zhong M, Feng L-F, et al. Silencing of Bcl-XL expression in human MGC-803 gastric cancer cells by siRNA. Acta Biochim Biophys Sin (Shanghai), 2005; 37(8):555–560.
209. Yuan W, Wu S, Guo J, et al. Silencing of TKTL1 by siRNA inhibits proliferation of human gastric cancer cells in vitro and in vivo. Cancer Biol Ther, 2010; 9(9):710–716.
210. Jafari Sani M, Yazdi F, Masoomi Karimi M, et al. The siRNA-Mediated down-regulation of vascular endothelial growth factor Receptor1. Iran Red Crescent Med J, 2016; 18(4):e23418.
211. Yu Q, Shang LU, Yu H, et al. Silencing of FRAT1 by siRNA inhibits the proliferation of SGC7901 human gastric adenocarcinoma cells. Biomed Rep, 2016; 4(2):223–226.
212. Fan C, Liu J, Tian J, et al. siRNA Targeting of the SNCG gene inhibits the growth of gastric carcinoma SGC7901 cells in vitro and in vivo by downregulating the phosphorylation of AKT/ERK. Cytogenet Genome Res, 2018; 154(4):209–216.
213. Wei J, Wang R, Lu Y, et al. Flotillin-1 promotes progression and dampens chemosensitivity to cisplatin in gastric cancer via ERK and AKT signaling pathways. Eur J Pharmacol, 2022; 916:174631.
214. Kang M, Ren MP, Zhao L, et al. miR-485-5p acts as a negative regulator in gastric cancer progression by targeting flotillin-1. Am J Transl Res, 2015; 7(11):2212–2222.
215. Si W, Shen J, Zheng H, et al. The role and mechanisms of action of microRNAs in cancer drug resistance. Clin Epigenetics, 2019; 11(1):25.
216. Zhang Y, Jia D-D, Zhang Y-F, et al. The emerging function and clinical significance of circRNAs in Thyroid Cancer and Autoimmune Thyroid Diseases. Int J Biol Sci, 2021; 17(7):1731–1741.
217. Min HY, Lee HY. Mechanisms of resistance to chemotherapy in non-small cell lung cancer. Arch Pharm Res, 2021; 44(2):146–164.
218. Ashrafizaveh S, Ashrafizadeh M, Zarrabi A, et al. Long non-coding RNAs in the doxorubicin resistance of cancer cells. Cancer Lett, 2021; 508:104–114.
219. Ashrafizadeh M, Delfi M, Hashemi F, et al. Biomedical application of chitosan-based nanoscale delivery systems: Potential usefulness in siRNA delivery for cancer therapy. Carbohydr Polym, 2021; 260:117809.
220. Abadi AJ, Mirzaei S, Mahabady MK, et al. Curcumin and its derivatives in cancer therapy: Potentiating antitumor activity of cisplatin and reducing side effects. Phytother Res, 2022; 36(1):189–213.
221. Hong L, Ning X, Shi Y, et al. Reversal of multidrug resistance of gastric cancer cells by down-regulation of ZNRD1 with ZNRD1 siRNA. Br J Biomed Sci, 2004; 61(4):206–210.
222. Han Z, Hong L, Wu K, et al. Reversal of multidrug resistance of gastric cancer cells by downregulation of Akt1 with Akt1 siRNA. J Exp Clin Cancer Res, 2006; 25(4):601–606.
223. Yuan H-H, Yang Y-N, Zhou J-H, et al. siRNA-mediated inactivation of HER3 improves the antitumour activity and sensitivity of gefitinib in gastric cancer cells. Oncotarget, 2017; 8(32):52584–52593.
224. Li BP, Liu JL, Chen JQ, et al. Effects of siRNA-mediated silencing of myeloid cell leukelia-1 on the biological behaviors and drug resistance of gastric cancer cells. Am J Transl Res, 2015; 7(11):2397–2411.
225. Wu Q, Gou Y, Wang Q, et al. Downregulation of RPL6 by siRNA inhibits proliferation and cell cycle progression of human gastric cancer cell lines. PLoS One, 2011; 6(10):e26401.
226. Li R, Chen WC, Pang XQ, et al. Combined effect of sCD40L and PI3K siRNA on transplanted tumours growth and microenvironment in nude mice with gastric cancer. Mol Biol Rep, 2012; 39(9):8755–8761.
227. Tan B, Li Y, Zhao Q, et al. Inhibition of gastric cancer cell growth and invasion through siRNA-mediated knockdown of guanine nucleotide exchange factor Vav3. Tumour Biol, 2014; 35(2):1481–1488.
228. Liu Z, Shen L, Xu L, et al. Down-regulation of β-1,3-N-acetylglucosaminyltransferase-8 by siRNA inhibits the growth of human gastric cancer. Mol Med Rep, 2011; 4(3):497–503.
229. Bian Y, Guo J, Qiao L, et al. miR-3189-3p mimics enhance the effects of S100A4 siRNA on the inhibition of proliferation and migration of gastric cancer cells by targeting CFL2. Int J Mol Sci, 2018; 19(1):236.
230. Yuan HF, Li Y, Tan BB, et al. Inhibitory effect of siRNA-Annexin A7 on growth, migration, and invasion in BGC823 cells and gastric cancer xenograftsin nude mice. Int J Clin Exp Pathol, 2020; 13(2):122–131.
231. Cai L, Ma X, Huang Y, et al. Aberrant histone methylation and the effect of Suv39H1 siRNA on gastric carcinoma. Oncol Rep, 2014; 31(6):2593–2600.
232. He X-W, Liu T, Chen Y-X, et al. Calcium carbonate nanoparticle delivering vascular endothelial growth factor-C siRNA effectively inhibits lymphangiogenesis and growth of gastric cancer in vivo. Cancer Gene Ther, 2008; 15(3):193–202.
233. Foulkes R, Man E, Thind J, et al. The regulation of nanomaterials and nanomedicines for clinical application: Current and future perspectives. Biomater Sci, 2020; 8(17):4653–4664.
234. Scioli Montoto S, Muraca G, Ruiz ME. Solid lipid nanoparticles for drug delivery: Pharmacological and biopharmaceutical aspects. Front Mol Biosci, 2020; 7:587997.
235. Mosquera J, García I, Liz-Marzán LM. Cellular uptake of nanoparticles versus small molecules: a matter of size. Acc Chem Res, 2018; 51(9):2305–2313.
236. Hamdy NM, Boseila AA, Ramadan A, et al. Iron oxide nanoparticles-plant insignia synthesis with favorable biomedical activities and less toxicity, in the “Era of the-Green”: A systematic review. Pharmaceutics, 2022; 14(4):844.
237. Alghamdi MA, Fallica AN, Virzì N, et al. The promise of nanotechnology in personalized medicine. J Pers Med, 2022; 12(5):673.
238. Aldea M, Orillard E, Mansi L, et al. How to manage patients with corticosteroids in oncology in the era of immunotherapy? Eur J Cancer, 2020; 141:239–251.
239. Karahmet Sher E, Alebić M, Marković Boras M, et al. Nanotechnology in medicine revolutionizing drug delivery for cancer and viral infection treatments. Int J Pharm, 2024; 660:124345.
240. Yang L, Du Y-E, Liao F, et al. A novel combined therapeutic strategy of Nano-EN-IR@Lip mediated photothermal therapy and stem cell inhibition for gastric cancer. Biomed Pharmacother, 2024; 174:116486.
241. Xu X, Wang L, Xu HQ, et al. Clinical comparison between paclitaxel liposome (Lipusu®) and paclitaxel for treatment of patients with metastatic gastric cancer. Asian Pac J Cancer Prev, 2013; 14(4):2591–2594.
242. Rizk NI, Kassem DH, Abulsoud AI, et al. Revealing the role of serum exosomal novel long non-coding RNA NAMPT-AS as a promising diagnostic/prognostic biomarker in colorectal cancer patients. Life Sci, 2024; 352:122850.
243. Zhang L, Xue Y, Zhang H. Suppression of gastric cancer cell proliferation by miR-494-3p inhibitor-loaded engineered exosomes. Heliyon, 2024; 10(10):e30803.
244. Ouyang Y, Zhou M, Liu Y, et al. Mg-doped ZnO nanoparticle as an effective nanocarrier in delivery of 5-Fluorouracil anti-gastric cancer drug. J Mol Struct, 2024; 1314:138706.
245. Liu X, Zhou H, Veisi H, et al. Imatinib-loaded pectin-modified magnetic nanoparticles as a smart pH-responsive therapeutic system against proliferation of gastric cancer cell line. Inorg Chem Commun, 2024; 161:112022.
246. Rezaei N, Kazem Arki M, Miri-Lavasani Z, et al. Co-delivery of doxorubicin and paclitaxel via noisome nanocarriers attenuates cancerous phenotypes in gastric cancer cells. Eur J Pharm Biopharm, 2023; 188:33–47.
247. Lu Z, Pang T, Yin X, et al. Delivery of TSPAN1 siRNA by novel Th17 targeted cationic liposomes for gastric cancer intervention. J Pharm Sci, 2020; 109(9):2854–2860.
248. Xiong D, Liu Z, Bian T, et al. GX1-mediated anionic liposomes carrying adenoviral vectors for enhanced inhibition of gastric cancer vascular endothelial cells. Int J Pharm, 2015; 496(2):699–708.
249. Xie F-L, Huang Z-T, Bai L, et al. Antitumor activity studies of iridium (III) polypyridine complexes-loaded liposomes against gastric tumor cell in vitro. J Inorg Biochem, 2021; 225:111603.
250. Hamdy NM, Eskander G, Basalious EB. Insights on the dynamic innovative tumor targeted-nanoparticles-based drug delivery systems activation techniques. Int J Nanomedicine, 2022; 17:6131–6155.
251. Namiki Y, Namiki T, Date M, et al. Enhanced photodynamic antitumor effect on gastric cancer by a novel photosensitive stealth liposome. Pharmacol Res, 2004; 50(1):65–76.
252. Shi J, Liu S, Yu Y, et al. RGD peptide-decorated micelles assembled from polymer-paclitaxel conjugates towards gastric cancer therapy. Colloids Surf B Biointerfaces, 2019; 180:58–67.
253. Li X, Yu N, Li J, et al. Novel “Carrier-Free” nanofiber Codelivery systems with the synergistic antitumor effect of paclitaxel and Tetrandrine through the enhancement of mitochondrial apoptosis. ACS Appl Mater Interfaces, 2020; 12(9):10096–10106.
254. Zhang C, Huang P, Bao L, et al. Enhancement of gastric cell radiation sensitivity by chitosan-modified gold nanoparticles. J Nanosci Nanotechnol, 2011; 11(11):9528–9535.
255. Huang P, Yang D-P, Zhang C, et al. Protein-directed one-pot synthesis of Ag microspheres with good biocompatibility and enhancement of radiation effects on gastric cancer cells. Nanoscale, 2011; 3(9):3623–3626.
256. Yang Z, Wang J, Liu S, et al. Defeating relapsed and refractory malignancies through a nano-enabled mitochondria-mediated respiratory inhibition and damage pathway. Biomaterials, 2020; 229:119580.
257. Zhang A, Pan S, Zhang Y, et al. Carbon-gold hybrid nanoprobes for real-time imaging, photothermal/photodynamic and nanozyme oxidative therapy. Theranostics, 2019; 9(12):3443–3458.
258. Miao Y-H, Mao L-P, Cai X-J, et al. Zinc oxide nanoparticles reduce the chemoresistance of gastric cancer by inhibiting autophagy. World J Gastroenterol, 2021; 27(25):3851–3862.
259. Zheng H, Chen Z, Cai A, et al. Nanoparticle mediated codelivery of nifuratel and doxorubicin for synergistic anticancer therapy through STAT3 inhibition. Colloids Surf B Biointerfaces, 2020; 193:111109.
260. Long Y, Wang Z, Fan J, et al. A hybrid membrane coating nanodrug system against gastric cancer via the VEGFR2/STAT3 signaling pathway. J Mater Chem B, 2021; 9(18):3838–3855.
261. Kanaya N, Kuroda S, Kubota T, et al. Novel therapeutic strategy for human epidermal growth factor receptor 2-positive gastric cancer. Gan To Kagaku Ryoho, 2017; 44(10):883–885.
262. Rezaul Islam M, Rauf A, Akash S, et al. Recent perspective on the potential role of phytocompounds in the prevention of gastric cancer. Process Biochemistry, 2023; 135:83–101.
263. Zhao M, Yang Y, Nian Q, et al. Phytochemicals and mitochondria: Therapeutic allies against gastric cancer. Phytomedicine, 2023; 110:154608.
264. Chen Y-C, Chiang Y-F, Lin Y-J, et al. Effect of vitamin D supplementation on primary dysmenorrhea: A systematic review and meta-analysis of randomized clinical trials. Nutrients, 2023; 15(13):2830.
265. Wang Y, Yuan A-J, Wu Y-J, et al. Silymarin in cancer therapy: Mechanisms of action, protective roles in chemotherapy-induced toxicity, and nanoformulations. J Funct Foods, 2023; 100:105384.
266. Wang YX, Cai H, Jiang G, et al. Silibinin inhibits proliferation, induces apoptosis and causes cell cycle arrest in human gastric cancer MGC803 cells via STAT3 pathway inhibition. Asian Pac J Cancer Prev, 2014; 15(16):6791–6798.
267. Rouhi AA, Valizadeh A, Sedghizadeh N, et al. Targeted therapy of gastric cancer with gingerol-loaded hyaluronic acid/PEG-coated PLGA nanoparticles: Development and physicochemical evaluation. J Drug Deliv Sci Technol, 2024; 97:105734.
268. Zhou H, Hu X, Li N, et al. Loganetin and 5-fluorouracil synergistically inhibit the carcinogenesis of gastric cancer cells via down-regulation of the Wnt/β-catenin pathway. J Cell Mol Med, 2020; 24(23):13715–13726.
269. Ham I-H, Wang L, Lee D, et al. Curcumin inhibits the cancer-associated fibroblast-derived chemoresistance of gastric cancer through the suppression of the JAK/STAT3 signaling pathway. Int J Oncol, 2022; 61(1):85.
270. Zheng R, Deng Q, Liu Y, et al. Curcumin inhibits gastric carcinoma cell growth and induces apoptosis by suppressing the Wnt/β-Catenin signaling pathway. Med Sci Monit, 2017; 23:163–171.
271. Xu J, Chen Y, Yang R, et al. Cucurbitacin B inhibits gastric cancer progression by suppressing STAT3 activity. Arch Biochem Biophys, 2020; 684:108314.
272. Yu D, Shin HS, Lee YS, et al. Genistein attenuates cancer stem cell characteristics in gastric cancer through the downregulation of Gli1. Oncol Rep, 2014; 31(2):673–678.
273. Wen Z, Feng S, Wei L, et al. Evodiamine, a novel inhibitor of the Wnt pathway, inhibits the self-renewal of gastric cancer stem cells. Int J Mol Med, 2015; 36(6):1657–1663.
274. Dang Y, Liu T, Yan J, et al. Gastric cancer proliferation and invasion is reduced by macrocalyxin C via activation of the miR-212-3p/Sox6 pathway. Cell Signal, 2020; 66:109430.
275. Shen X, Si Y, Wang Z, et al. Quercetin inhibits the growth of human gastric cancer stem cells by inducing mitochondrial-dependent apoptosis through the inhibition of PI3K/Akt signaling. Int J Mol Med, 2016; 38(2):619–626.
276. Lee C-H, Tsai H-Y, Chen C-L, et al. Isoliquiritigenin inhibits gastric cancer stemness, modulates tumor microenvironment, and suppresses tumor growth through glucose-regulated protein 78 downregulation. Biomedicines, 2022; 10(6):1350.
277. Qi X, Liu J, Wang L, et al. Kaempferol-induced mitochondrial damage promotes NF-κB-NLRP3-caspase-1 signaling axis-mediated pyroptosis in gastric cancer cells. Heliyon, 2024; 10(7):e28672.
278. Huang N, He H-W, He Y-y, et al. Xiaotan Sanjie recipe, a compound Chinese herbal medicine, inhibits gastric cancer metastasis by regulating GnT-V-mediated E-cadherin glycosylation. J Integr Med, 2023; 21(6):561–574.
279. Fang S-Q, Liu Y-H, Zhao K-P, et al. Transcriptional profiling and network pharmacology analysis identify the potential biomarkers from Chinese herbal formula Huosu Yangwei Formula treated gastric cancer in vivo. Chin J Nat Med, 2021; 19(12):944–953.
280. Song S-J, Liu X, Ji Q, et al. Ziyin Huatan Recipe, a Chinese herbal compound, inhibits migration and invasion of gastric cancer by upregulating RUNX3 expression. J Integr Med, 2022; 20(4):355–364.
281. Tibenda JJ, Du Y, Nan Y, et al. Astragalus mongholicus: A review of its pharmacological mechanisms against gastric cancer. J Herb Med, 2024; 45:100881.
282. Wang Y, Li J, Liu X, et al. Elucidation of the anti-gastric cancer mechanism of Guiqi Baizhu Formula by integrative approach of chemical bioinformatics. Int Immunopharmacol, 2024; 134:112245.
283. Deng Y-Q, Gao M, Lu D, et al. Compound-composed Chinese medicine of Huachansu triggers apoptosis of gastric cancer cells through increase of reactive oxygen species levels and suppression of proteasome activities. Phytomedicine, 2024; 123:155169.
284. Zhang Z, Wu C, Liu N, et al. Modified Banxiaxiexin decoction benefitted chemotherapy in treating gastric cancer by regulating multiple targets and pathways. J Ethnopharmacol, 2024; 331:118277.
285. Le TTH, Ngo TH, Nguyen TH, et al. Anti-cancer activity of green synthesized silver nanoparticles using Ardisia gigantifolia leaf extract against gastric cancer cells. Biochem Biophys Res Commun, 2023; 661:99–107.
286. Zhang R, Chen X, Miao C, et al. Tumor-associated macrophage-derived exosomal miR-513b-5p is a target of jianpi yangzheng decoction for inhibiting gastric cancer. J Ethnopharmacol, 2024; 318(Pt B):117013.
287. Long J, Wang W, Chu J, et al. Overexpression of Nrf2 reverses ferroptosis induced by Arenobufagin in gastric cancer. Toxicol Appl Pharmacol, 2024; 484:116842.
288. Zhang M, Ding Y, Hu S, et al. Transcriptomics and systems network-based molecular mechanism of herbal formula Huosu-Yangwei inhibited gastric cancer in vivo. J Ethnopharmacol, 2023; 316:116674.
289. Yu J-R, Liu Y-Y, Gao Y-Y, et al. Diterpenoid tanshinones inhibit gastric cancer angiogenesis through the PI3K/Akt/mTOR signaling pathway. J Ethnopharmacol, 2024; 324:117791.
290. Chu Z, Zhu M, Luo Y, et al. Terpene extract from the stem of Celastrus orbiculatus inhibits actin cytoskeleton remodelling in gastric cancer cells by regulating the protein interaction between PTBP1 and ACTN4. J Pharm Anal, 2024; 14(8):101021.
291. Kai K, Han-Bing J, Bing-Lin C, et al. Network pharmacology, molecular docking and experimental verification help unravel chelerythrine’s potential mechanism in the treatment of gastric cancer. Heliyon, 2023; 9(7):e17393.
292. Ou L, Li M, Hou Y. Network pharmacology, bioinformatics, and experimental validation to identify the role of Hedyotis diffusa willd against gastric cancer through the activation of the endoplasmic reticulum stress. Heliyon, 2024; 10(7):e28833.
293. Janiczek-Polewska M, Szylberg Ł, Malicki J, et al. Role of interleukins and new perspectives in mechanisms of resistance to chemotherapy in gastric cancer. Biomedicines, 2022; 10(7):1600.
294. Liu J, Yuan Q, Guo H, et al. Deciphering drug resistance in gastric cancer: Potential mechanisms and future perspectives. Biomed Pharmacother, 2024; 173:116310.
295. Bukowski K, Kciuk M, Kontek R. Mechanisms of multidrug resistance in cancer chemotherapy. Int J Mol Sci, 2020; 21(9):3233.
296. Xiao F, Ouyang B, Zou J, et al. Trim14 promotes autophagy and chemotherapy resistance of gastric cancer cells by regulating AMPK/mTOR pathway. Drug Dev Res, 2020; 81(5):544–550.
297. Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell, 2012; 149(5):1060–1072.
298. Chen X, Kang R, Kroemer G, et al. Broadening horizons: The role of ferroptosis in cancer. Nat Rev Clin Oncol, 2021; 18(5):280–296.
299. Yang WS, SriRamaratnam R, Welsch ME, et al. Regulation of ferroptotic cancer cell death by GPX4. Cell, 2014; 156(1–2):317–331.
300. Zou S, Tong Q, Liu B, et al. Targeting STAT3 in cancer immunotherapy. Mol Cancer, 2020; 19(1):145.
301. Zhang X, Huang T, Li Y, et al. Upregulation of THBS1 is related to immunity and chemotherapy resistance in gastric cancer. Int J Gen Med, 2021; 14:4945–4957.
302. Gu J, Li X, Zhao L, et al. The role of PKM2 nuclear translocation in the constant activation of the NF-κB signaling pathway in cancer-associated fibroblasts. Cell Death Dis, 2021; 12(4):291.
303. Komander D, Rape M. The ubiquitin code. Annu Rev Biochem, 2012; 81:203–229.
304. Deng L, Meng T, Chen L, et al. The role of ubiquitination in tumorigenesis and targeted drug discovery. Signal Transduct Target Ther, 2020; 5(1):11.
305. Akrami H, Moradi B, Borzabadi Farahani D, et al. Ibuprofen reduces cell proliferation through inhibiting Wnt/β catenin signaling pathway in gastric cancer stem cells. Cell Biol Int, 2018; 42(8):949–958.
306. Cao W, Li Y, Sun H, et al. Apatinib suppresses gastric cancer stem cells properties by inhibiting the Sonic Hedgehog pathway. Front Cell Dev Biol, 2021; 9:679806.
307. Ham I-H, Oh HJ, Jin H, et al. Targeting interleukin-6 as a strategy to overcome stroma-induced resistance to chemotherapy in gastric cancer. Mol Cancer, 2019; 18(1):68.
308. Huang W, Wen F, Yang P, et al. Yi-qi-hua-yu-jie-du decoction induces ferroptosis in cisplatin-resistant gastric cancer via the AKT/GSK3β/NRF2/GPX4 axis. Phytomedicine, 2024; 123:155220.
309. Anitha K, Chenchula S, Surendran V, et al. Advancing cancer theranostics through biomimetics: A comprehensive review. Heliyon, 2024; 10(6):e27692.
310. Chen Y, Lian G, Liao C, et al. Characterization of polyethylene glycol-grafted polyethylenimine and superparamagnetic iron oxide nanoparticles (PEG-g-PEI-SPION) as an MRI-visible vector for siRNA delivery in gastric cancer in vitro and in vivo. J Gastroenterol, 2013; 48(7):809–821.
311. Chen Y, Wang W, Lian G, et al. Development of an MRI-visible nonviral vector for siRNA delivery targeting gastric cancer. Int J Nanomedicine, 2012; 7:359–368.
312. Huang P, Li Z, Lin J, et al. Photosensitizer-conjugated magnetic nanoparticles for in vivo simultaneous magnetofluorescent imaging and targeting therapy. Biomaterials, 2011; 32(13):3447–3458.
313. Huang P, Lin J, Wang X, et al. Light-triggered theranostics based on photosensitizer-conjugated carbon dots for simultaneous enhanced-fluorescence imaging and photodynamic therapy. Adv Mater, 2012; 24(37):5104–5110.
314. Li R, Liu B, Gao J. The application of nanoparticles in diagnosis and theranostics of gastric cancer. Cancer Lett, 2017; 386:123–130.
315. Lozano N, Al-Ahmady ZS, Beziere NS, et al. Monoclonal antibody-targeted PEGylated liposome-ICG encapsulating doxorubicin as a potential theranostic agent. Int J Pharm, 2015; 482(1–2):2–10.
316. Mariano RN, Alberti D, Cutrin JC, et al. Design of PLGA based nanoparticles for imaging guided applications. Mol Pharm, 2014; 11(11):4100–4106.
317. Yao H, Xu K, Zhou J, et al. A tumor microenvironment destroyer for efficient cancer suppression. ACS Biomater Sci Eng, 2020; 6(1):450–462.
318. Liu D, Li X, Chen C, et al. Target-specific delivery of oxaliplatin to HER2-positive gastric cancer cells in vivo using oxaliplatin-au-fe3o4-herceptin nanoparticles. Oncol Lett, 2018; 15(5):8079–8087.
319. Meng X, Wang K, Lv L, et al. Photothermal/Photodynamic therapy with immune‐adjuvant liposomal complexes for effective gastric cancer therapy. Part & Part Syst Charact, 2019; 36(6):1900015.
320. Liu Q, Li R-T, Qian H-Q, et al. Gelatinase-stimuli strategy enhances the tumor delivery and therapeutic efficacy of docetaxel-loaded poly(ethylene glycol)-poly(ɛ-caprolactone) nanoparticles. Int J Nanomedicine, 2012; 7:281–295.
321. Cui F-B, Li R-T, Liu Q, et al. Enhancement of radiotherapy efficacy by docetaxel-loaded gelatinase-stimuli PEG-Pep-PCL nanoparticles in gastric cancer. Cancer Lett, 2014; 346(1):53–62.
322. Wu F-L, Li R-T, Yang M, et al. Gelatinases-stimuli nanoparticles encapsulating 5-fluorouridine and 5-aza-2’-deoxycytidine enhance the sensitivity of gastric cancer cells to chemical therapeutics. Cancer Lett, 2015; 363(1):7–16.
323. Sun Z, Song X, Li X, et al. In vivo multimodality imaging of miRNA-16 iron nanoparticle reversing drug resistance to chemotherapy in a mouse gastric cancer model. Nanoscale, 2014; 6(23):14343–14353.
324. Portillo-Miño JD, Bettin-Gonzalez D, Coral FAM. mRNA vaccines in gastric cancer: How close are we? Vacunas (English Edition), 2024; 25(1):88–96.
325. Yu MZ, Wang NN, Zhu JQ, et al. The clinical progress and challenges of mRNA vaccines. Wiley Interdiscip Rev Nanomed Nanobiotechnol, 2023; 15(5):e1894.
326. Cheng F, Wang Y, Bai Y, et al. Research advances on the stability of mRNA vaccines. Viruses, 2023; 15(3):668.
327. Zhang A, Ji Q, Sheng X, et al. mRNA vaccine in gastrointestinal tumors: Immunomodulatory effects and immunotherapy. Biomed Pharmacother, 2023; 166:115361.
328. Han G, Noh D, Lee H, et al. Advances in mRNA therapeutics for cancer immunotherapy: From modification to delivery. Adv Drug Deliv Rev, 2023; 199:114973.
329. Sun H, Zhang Y, Wang G, et al. mRNA-Based therapeutics in cancer treatment. Pharmaceutics, 2023; 15(2):622.
330. You W, Ouyang J, Cai Z, et al. Comprehensive analyses of immune subtypes of stomach adenocarcinoma for mRNA vaccination. Front Immunol, 2022; 13:827506.
331. Gastric Cancer. US Government, 2024.
Cite
Cite
Cite
OR
Download to reference manager
If you have citation software installed, you can download citation data to the citation manager of your choice
Information, rights and permissions
Information
Published In
Article first published online: December 23, 2025
Keywords
Authors
Metrics and citations
Metrics
Journals metrics
This article was published in Cancer Biotherapy and Radiopharmaceuticals.
View All Journal MetricsPublication usage*
Total views and downloads: 360
*Publication usage tracking started in December 2016
Publications citing this one
Receive email alerts when this publication is cited
Web of Science: 0
Crossref:
There are no citing articles to show.
Figures and tables
Figures & Media
Tables
View Options
Access options
If you have access to journal content via a personal subscription, university, library, employer or society, select from the options below:
I am signed in as:
View my profileSign out
I can access personal subscriptions, purchases, paired institutional access and free tools such as favourite journals, email alerts and saved searches.
loading institutional access options
Alternatively, view purchase options below:
Purchase 24 hour online access to view and download content.
Access journal content via a DeepDyve subscription or find out more about this option.
